Doença granulomatosa crônica: características clínicas, seguimento e terapêutica de cinco pacientes pediátricos / Chronic granulomatous disease: clinical characteristics, follow-up, and therapy of 5 pediatric patients

Introdução: A doença granulomatosa crônica (DGC) é caracterizada por um defeito na capacidade microbicida das células fagocíticas (monócitos e neutrófilos), com alta mortalidade se não diagnosticada precocemente. Os pacientes apresentam infecções recorrentes ou graves, suscetibilidade a granulomas em órgãos profundos, doenças autoimunes e doença inflamatória intestinal. Objetivo e Método: Relato de aspectos clínicos e do tratamento de cinco pacientes com doença granulomatosa crônica. Resultados: Cinco pacientes, três meninos, medianas de idade no início dos sintomas e diagnóstico de 8 meses e 48 meses, respectivamente, foram estudados por um período de 10 anos. Pneumonia (5/5) e doença micobacteriana (3/5) foram as manifestações iniciais mais comuns. Alterações pulmonares foram observadas em todos os casos. Mutações nos genes CYBB e NCF1 foram identificadas em três casos. Antibioticoprofilaxia foi instituída em todos os pacientes e três foram submetidos ao transplante de células tronco-hematopoiéticas (TCH), aos 7, 18 e 19 anos e com sobrevida atual entre 4 a 5 anos. Conclusão: O monitoramento cuidadoso de infecções graves com tratamento imediato foi crucial para a sobrevivência. O TCH, mesmo ao final da adolescência, promoveu a cura da DGC em três pacientes.

Introduction: Chronic granulomatous disease (CGD) is characterized by a defective microbicidal capacity of phagocytic cells (monocytes and neutrophils) with high mortality if not early diagnosed. Patients have recurrent or severe infections and are susceptible to granulomas in visceral organs, autoimmune diseases, and inflammatory bowel diseases. Objective and Method: To report the clinical features and treatment of 5 patients with CGD. Results: Five patients, 3 boys, with median ages at symptom onset and diagnosis of 8 months and 48 months, respectively, were followed for 10 years. Pneumonia (5/5) and mycobacterial disease (3/5) were the most common initial manifestations. Pulmonary changes were observed in all cases. Mutations in the CYBB and NCF1 genes were identified in 3 cases. All patients received antibiotic prophylaxis. Three patients underwent a hematopoietic stem cell transplant (HSCT) at 7, 18, and 19 years, with current survival of 4 to 5 years. Conclusion: Careful monitoring for severe infection with prompt treatment was crucial for survival. Even though HSCT was performed in late adolescence, it promoted the cure of CGD in 3 patients.

Abscesos cerebrales por Dermacoccus nishinomiyaensis como primera manifestación de enfermedad granulomatosa crónica / Dermacoccus nishinomiyaensis brain abscesses as the first manifestation of chronic granulomatous disease

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria poco frecuente, que secaracteriza por defectos en alguna de las subunidades del complejo enzimático nicotinamida adeninadinucleótido fosfato oxidasa, que ocasiona un déficit en la generación de anión superóxido por losfagocitos. Dentro de este grupo, la forma ligada al X es la más frecuente. Se reporta el caso de una paciente de sexo femenino de 2 años con enfermedad granulomatosa crónica autosómica recesiva, con mutación en gen CYBA, quien presentó manifestación inicial de la enfermedad con abscesos cerebrales ocasionados por un germen oportunista (Dermacoccus nishinomiyaensis). Esta infección permitió la sospecha diagnóstica temprana, por lo que recibió el tratamiento y la profilaxis en forma oportuna. Actualmente, se encuentra libre de infecciones, a la espera del trasplante de células progenitoras hematopoyéticas.

Chronic granulomatous disease is a rare primary immunodeficiency characterized by defects in one of the subunits of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, which causes a deficiency in the capacity of phagocytes to generate superoxide anion. Within this group, the X-linked form is the most frequent. Here we report the case of a 2-year-old female patient with autosomal recessive chronic granulomatous disease, with a mutation in the CYBA gene, whose initial manifestation was brain abscesses caused by an opportunistic microorganism (Dermacoccus nishinomiyaensis). The infection led to an early diagnostic suspicion, so treatment and prophylaxis were administered in a timely manner. Currently, she is infectionfree, awaiting hematopoietic progenitor cell transplantation.

Sarcoidosis cutánea. Presentación de un caso

La sarcoidosis es una enfermedad granulomatosa sistémica de causa desconocida, con mayor prevalencia en el sexo femenino, entre los 20 a 40 años de edad; caracterizada por la formación de granulomas no caseificantes en distintos órganos. La afectación cutánea de forma exclusiva es rara, pues se describe solo en el 4-5 % de los pacientes, ya que las lesiones en piel pueden aparecer antes o después del compromiso sistémico, o bien coincidir con este. Se presenta el caso de una paciente de 35 años con lesiones en piel de cuatro años de evolución. Considerando el cuadro clínico y la histopatología, se concluyó con el diagnóstico de sarcoidosis cutánea, crónica y asintomática. Se trata de una enfermedad muy polimorfa en sus manifestaciones cutáneas, lo cual la convierte en una gran simuladora, y su diagnóstico constituye un reto para el dermatólogo.

Sarcoidosis is a systemic granulomatous disease of unknown cause, with a higher prevalence in females, between 20 and 40 years of age; characterized by the formation of non-caseating granulomas in different organs. Exclusive skin involvement is rare, as it is described in only 4-5% of patients, since skin lesions may appear before or after systemic involvement, or coincide with it. The case of a 35-years-old patient with skin lesions of four years of evolution is presented. Considering the clinical case and histopathology, the diagnosis of chronic and asymptomatic cutaneous sarcoidosis was concluded. It is a very polymorphic disease in its skin manifestations, which makes it a great simulator, and its diagnosis constitutes a challenge for the dermatologist.

Dermoscopy of cutaneous sarcoidosis: a cross-sectional study

Abstract Background Although traditionally used for the diagnosis of skin tumors, in the past few years dermoscopy as a clinical diagnostic aid for inflammatory and infectious skin manifestations has also received more and more attention. The clinical variability of cutaneous sarcoidosis (CS) often makes its correct diagnosis challenging. Dermoscopy can be used as an auxiliary examination method. Objective Our aim was to evaluate the role of dermoscopy in the diagnosis and differential diagnosis of CS. Methods This was a retrospective analysis of 39 CS clinical and dermoscopic images collected in the Department of Dermatology, Huashan Hospital Affiliated with Fudan University from August 2013 to February 2021. Results Retrospective dermoscopic evaluation revealed small grouped, translucent orange globular structures in all 39 cases. Variable diameter linear vessels were found in 38 cases. A central scar-like area was seen in 26 cases. Bright white streaks were seen in 30 cases. The follicular plugs were seen in 15 cases. Study limitations First, the number of cutaneous sarcoidosis cases the authors collected is small. Second, due to the lack of a control group, the sensitivity and specificity of the proposed criteria were not calculated. Finally, since our study mainly includes suspicious lesions that were biopsied for diagnostic purposes, there may be a selection bias. Conclusion Lesions showing on dermoscopy grouped translucent orange ovoid structures associated with linear vessels should raise the suspicion of CS. Central scar-like areas and bright white streaks are also helpful in the diagnosis of CS.

Epidemiological characterization of patients with sarcoidosis in a high complexity hospital in southwestern Colombia

Introduction: Epidemiological studies on sarcoidosis in Colombia are scarce, and although recent reports from the north of the country have been published, clinical-epidemiological associations are not clear. Our aim was to characterize patients with sarcoidosis diagnosed at Fundación Valle del Lili in Cali, Colombia. Methods: A retrospective study of a series of sarcoidosis cases was conducted between 2011 and 2019. Demographic, clinical, laboratory, imaging, histopathological, and treatment variables were analyzed. Results: A total of 34 patients with a diagnosis of sarcoidosis were found. The majority were women (n = 25; 73%), and the mean age was 50 years. The main symptoms of onset were erythema nodosum (n = 11; 33%), arthritis (n = 10; 30%), and cough (n = 9; 27%). In 64% of the cases, there was pulmonary involvement, with pulmonary nodules, mediastinal adenopathy, and interstitial lung disease found in 54%, 50%, and 36% of cases, respectively. In 85% of cases, there were extrapulmonary manifestations, mainly cutaneous (50%). Angiotensin-converting enzyme (ACE) was elevated in 62% of the cases in which it was measured (n = 16; 47%). During the diagnostic process, 23 biopsies were performed, of which 95% showed granulomas with noncaseating necrosis. Most of the patients (76%) were controlled with prednisolone, at an average dose of 20 mg (7.5-50 mg) per day. Conclusions: Sarcoidosis was more frequent in women and mestizos, and it presented earlier in men. Elevated ACE was not associated with extrapulmonary involvement. Calcium-phosphorus profile and antinuclear antibodies were not useful to establish the diagnosis.

Introducción: En Colombia son escasos los estudios epidemiológicos sobre la sarcoidosis; aunque recientemente se han publicado reportes del norte del país, son grupos muestrales pequeños, por lo que no quedan claras las asociaciones clínico-epidemiológicas. Nuestro objetivo fue caracterizar pacientes con sarcoidosis en la Fundación Valle del Lili, en Cali, Colombia. Métodos: Se realizó un estudio retrospectivo de una serie de casos de sarcoidosis entre el 2011 y el 2019. Se analizaron variables demográficas, clínicas, de laboratorio, imagenológicas, histopatológicas y de tratamiento. Resultados: Se encontraron 34 pacientes con diagnóstico de sarcoidosis, la mayoría fueron mujeres (n = 25; 73%), y la edad promedio fue 50 anos. Los principales síntomas de inicio fueron eritema nudoso (n = 11; 33%), artritis (n = 10; 30%) y tos (n = 9; 27%). En el 64% de los casos hubo compromiso pulmonar, y se encontraron nódulos pulmonares, adenopatías mediastinales y enfermedad pulmonar intersticial en un 54, 50 y 36% de los casos, respectivamente. En el 85% de los casos hubo manifestaciones extrapulmonares, principalmente cutáneas (50%). Los niveles de enzima conversora de angiotensina estuvieron elevados en el 62% de los casos en los que fue medida (n = 16; 47%). Durante el proceso diagnóstico se realizaron 23 biopsias, de las cuales el 95% evidenció granulomas con necrosis no caseificante. La mayoría de los pacientes (76%) fueron controlados con prednisolona, a una dosis promedio de 20 mg (7,5-50 mg) por día. Conclusiones: La sarcoidosis fue más frecuente en mujeres y mestizos. La presentación fue más temprana en hombres. La enzima conversora de angiotensina no se relacionó con compromiso extrapulmonar. Ni el perfil fósforo-calcio ni los anticuerpos antinucleares fueron útiles para establecer el diagnóstico.

Tuberculose intratorácica na forma pseudotumoral e óssea como manifestação de doença granulomatosa crônica / Intrathoracic tuberculosis in the pseudotumoral and bone form as a manifestation of chronic granulomatous disease

A doença granulomatosa crônica (DGC) é um erro inato da imunidade de fagócitos, e ocorre em decorrência de mutações que afetam componentes da enzima NADPH oxidase. Os pacientes são suceptíveis a infecções graves e letais por fungos e bactérias. O objetivo deste trabalho é relatar o caso de um lactente com DGC que apresentou manifestação clínica de tuberculose (TB) intratorácica na forma pseudotumoral e óssea iniciada no período neonatal. O diagnóstico de DGC foi realizado através do teste de DHR e, após o início da profilaxia com sulfametoxazoltrimetroprima e itraconazol, o paciente manteve-se estável clinicamente. A mãe e a irmã também apresentaram DHR alterados, a análise genética revelou uma mutação ligada ao X no exon 2 do gene CYBB c.58G>A, levando uma alteração em G20R. É fundamental que o diagnóstico seja realizado o mais precocemente possível, a fim de instituir as orientações aos familiares e tratamento adequado, reduzindo assim complicações infecciosas e melhorando prognóstico.

Chronic granulomatous disease (CGD) is an inborn error of phagocyte immunity and occurs as a resulto f mutations that affect components of the NADPH oxidase enzyme. Patients are susceptible to serious and lethal fungal and bacterial infections. The aim of this paper is to report a case an infant with CGD who presented clinical manifestations of intrathoracic tuberculosis (TB) in the pseudotumoral and bone form, which started in the neonatal period. The diagnosis of CGD was performed using the DHR test and, after starting prophylaxis with sulfamethoxazole-trimethoprim and itraconazole, the patient remained clinically stable. The mother and sister also had altered DHR, genetic analysis revealed an X-linked mutation in exon 2 of the CYBB gene c.58G>A, leading to an alteration in G20R. It is essential that the diagnosis is made as early as possible, in order to establish guidelines for Family members and adequate treatment, thus reducing infectious complications and improving prognosis.

Canine gastrointestinal pythiosis: a case report in Brazilian Pantanal from a diagnostic approach / Pitiose gastrointestinal canina: relato de caso no Pantanal brasileiro a partir de uma abordagem diagnóstica

Pythiosis is caused by an aquatic fungus-like organism (Pythium insidiosum). It is considered an important public health issue as it can affect both animals and humans. This paper reports a case of gastrointestinal pythiosis in a dog. The patient was hospitalized for four days, during which the animal received supportive and symptomatic treatment. But the applied treatment was unsuccessful and the dog's clinical condition worsened, culminating in death. Complementary imaging tests such as radiography and ultrasonography, as well as hematological tests, were performed during the hospitalization period. The definitive diagnosis was reached in the postmortem as macroscopic and microscopic characteristics suggested the presence of intestinal granuloma and accentuated multifocal suppurative necrotic enteritis. Additionally, the histological evaluation revealed morphological structures compatible with P. insidiosum. Also, the results of nested PCR performed showed partial amplification (105 bp) of the ITS1 region of the ribosomal gene of P. insidiosum.(AU)

A pitiose é causada por um organismo aquático semelhante a um fungo (Pythium insidiosum) e considerada um importante problema de saúde pública, pois pode afetar animais e humanos. Este artigo relata um caso de pitiose gastrointestinal em um cão. O paciente ficou internado por quatro dias, período em que o animal recebeu tratamento de suporte e sintomático. No entanto, o tratamento aplicado não teve sucesso e o quadro clínico do cão piorou, culminando com a morte. Exames de imagem complementares, como radiografia e ultrassonografia, bem como exames hematológicos, foram realizados durante o período de internação. O diagnóstico definitivo foi feito na autópsia, pois as características macroscópicas e microscópicas sugeriam a presença de granuloma intestinal e acentuada enterite necrótica multifocal supurativa. Além disso, a avaliação histológica revelou estruturas morfológicas compatíveis com P. insidiosum. Além disso, a nested PCR foi realizada e mostrou amplificação parcial (105 pb) da região ITS1 do gene ribossomal de P. insidiosum.(AU)

Female CYBB Mutation Mosaicism Leading to Inheritance of X-linked Chronic Granulomatous Disease / 罕见病研究

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

Osteomielitis multifocal por Serratia marcescens en un niño con enfermedad granulomatosa crónica / Serratia marcescens multifocal osteomyelitis in a child with chronic granulomatous disease

Resumen La enfermedad granulomatosa crónica (EGC) es una inmunode-ficiencia primaria poco frecuente. Se caracteriza por una alteración en la función de los fagocitos, causando infecciones recurrentes bacterianas y fúngicas. Presentamos el caso clínico de un niño con una osteomielitis multifocal por Serratia marcescens , microorganismo infrecuente como causa de infecciones óseas en niños, aunque asociado a la EGC. El estudio de infecciones con presentación clínica y agentes inhabituales deben hacer sospechar una EGC. Su diagnóstico precoz en la vida, así como el tratamiento antimicrobiano oportuno y el uso posterior de una profilaxis antimicrobiana adecuada logrará evitar recurrencias infecciosas y secuelas.

Abstract Chronic granulomatous disease (CGD) is a rare primary immuno-deficiency. It is characterized by an alteration in the function of phagocytes causing recurrent bacterial and fungal infections. This is a case report of a child with multifocal osteomyelitis by Serratia marcescens, an infrequent as a cause of bone infections, although associated with CGD. The study of infections with clinical presentation and unusual agents should lead to suspicion of CGD. The diagnosis early in life, as well as timely antimicrobial treatment and the subsequent antimicrobial prophylaxis will avoid infectious recurrences and sequelae.

Enfermedad granulomatosa crónica: fisiopatología genética y molecular. Pruebas diagnósticas vigentes / Chronic granulomatous disease: genetic and molecular pathophysiology. Effective diagnostic tests

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria congénita del sistema inmune innato, originada por defectos en el complejo enzimático nicotinamida adenina dinucleótido fosfato oxidasa presente en células fagocíticas. Estos defectos funcionales causan incapacidad para producir especies reactivas del oxígeno en los fagocitos, que afectan la eliminación de algunos microorganismos patógenos dentro del fagolisosoma. El diagnóstico de esta enfermedad se realiza actualmente mediante la prueba de 1,2,3-dihidrorodamina asistida por citometría de flujo multiparamétrica, o la tinción de fagocitos con nitroazul de tetrazolio asistida por microscopio óptico. Objetivos: Describir los aspectos fisiopatológicos y moleculares de la enfermedad granulomatosa crónica; y discutir aspectos relacionados con las pruebas de diagnóstico antes mencionadas. Métodos: Se realizó una investigación bibliográfica-documental a partir de artículos científicos publicados desde 1933 hasta 2018, para ello fueron consultadas las bases de datos SciELO, PubMed y Springer. Desarrollo: Se exponen las características fisiopatológicas de la enfermedad granulomatosa crónica, así como la relación entre las mutaciones genéticas más abundantes en la población afectada y la gravedad de las manifestaciones clínicas que presentan los pacientes. Además, se analizan críticamente los beneficios y las deficiencias de dos técnicas que se utilizan actualmente para diagnosticar la enfermedad. Conclusiones: La enfermedad granulomatosa crónica puede generar consecuencias inmunológicas e inflamatorias graves, que se hallan en consonancia con las características genéticas expresadas en el complejo enzimático dañado. El diagnóstico de la enfermedad resulta más confiable, exhaustivo y específico, mediante la citometría de flujo y su prueba de 1,2,3-dihidrorodamina(AU)

Introduction: Chronic granulomatous disease is a congenital primary immunodeficiency of the innate immune system, caused by defects in the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex present in phagocytic cells. These functional defects cause inability to produce reactive oxygen species in phagocytes, affecting the elimination of some pathogenic microorganisms within the phagolysosome. The diagnosis of this disease is currently made by means of the 1,2,3-dihydrorodamine test assisted by multiparametric flow cytometry, or the staining of phagocytes with nitro-blue tetrazolium assisted by light microscopy. Objectives: To characterize molecular and pathophysiologically the chronic granulomatous disease; and to discuss aspects related to the aforementioned diagnostic tests. Methods: In this work, a bibliographic-documentary research was carried out from scientific articles published from 1933 to 2018, for which the SciELO, PubMed and Springer databases were consulted. Development: The pathophysiological characteristics of chronic granulomatous disease are exposed, as well as the relationship between the most abundant genetic mutations in the affected population, and the severity of the clinical manifestations presented by the patients. In addition, the benefits and deficiencies of two techniques currently used to diagnose the disease are critically analyzed. Conclusions: Chronic granulomatous disease can generate severe immunological and inflammatory consequences, which are in line with the genetic characteristics expressed in the damaged enzyme complex. The diagnosis of the disease is more reliable, exhaustive and specific, using flow cytometry and its 1,2,3-dihydrorodamine test(AU)

Sarcoid-like granulomatous myositis-associated hypercalcemia. An infrequent case to consider / Hipercalcemia asociada a miositis granulomatosa sarcoidea simil- sarcoidea. Un caso infrecuente a considerar

Abstract PTH-independent hypercalcemia due to granulomatous disease is well-documented and sarcoidosis is the most characteristic disease, although there are others. We describe a case of sarcoid-like granulomatous myositis. An 87-year-old man was referred with tetraparesis and hypercalcemia (albumin-corrected calcium of 13.4 mg/dl) following a trip to the Caribbean. The evaluation showed a suppressed PTH, 25-hydroxy vitamin D of 7.5 ng/ml, 18F-FDG PET/CT showed markedly increased uptake in intercostal, back, shoulder, but tock and thigh muscles and a deltoid biopsy confirmed extensive granulomatous myositis. He was prescribed glucocorticoids which resulted in normalized plasma calcium levels and complete recovery from tetraparesis. Sarcoid-like granulomatous myositis should be incorporated into the differential diagnosis of PTH-independent hypercalcemia, especially in the absence of clinical features of sarcoidosis and with special emphasis on the use of 18F-FDG PET/CT to ensure a correct approach.

Resumen La hipercalcemia PTH-independiente asociada a enfermedades granulomatosas está bien documentada y la sarcoidosis es la enfermedad más característica, a pesar de que existen otras. Des cribimos un caso de miositis granulomatosa simil-sarcoidea. Un hombre de 87 años consultó por tetraparesia e hipercalcemia (calcio corregido por albúmina 13.4 mg/dl) luego de un viaje al Caribe. La evaluación mostró una PTH suprimida, 25-hidroxivitamina D 7.5 ng/ml, 18F-FDG PET/CT mostró marcado aumento de captación a nivel de musculatura intercostal, dorsal, deltoidea, glúteos y muslos. Una biopsia deltoidea confirmó una miositis granulomatosa extensa. Se prescribieron glucocorticoides, resultando en normalización del calcio plasmático y completa recuperación de la tetraparesia. La miositis granulomatosa simil-sarcoidea debe ser incorporada den tro del diagnóstico diferencial de la hipercalcemia PTH-independiente, especialmente en ausencia de hallazgos clínicos de sarcoidosis y con especial énfasis en el uso de 18F-FDG PET/CT para su correcta aproximación.

Granuloma anular maculoso / Patch granuloma annulare

El granuloma anular maculoso es una variante rara de granuloma anular, que representa un desafío diagnóstico. Su incidencia se desconoce y se presenta con mayor frecuencia en las mujeres de entre 40 y 70 años. Se asocia a las mismas entidades y responde a los mismos tratamientos que las otras variantes clínicas de granuloma anular. Se presentan los casos de 5 mujeres con diagnóstico de granuloma anular maculoso, que recibieron diferentes tratamientos tópicos y sistémicos, con respuestas clínicas variables.

Patch-type granuloma annulare is a rare variant of granuloma annulare, thus which represents diagnostic challenge. It has an unknown incidence and occurs most often in women between 40 and 70 years of age. It presents similar associations and responds to treatment as the clinical variants. We present 5 emale patients with patch-type granuloma annulare, who received different topical and systemic treatments, with variable clinical responses.

Treatments and prognosis of 82 children with chronic granulomatous disease in a single center / 中华实用儿科临床杂志

Objective:To summarize the treatments and outcomes of patients with chronic granulomatous disease (CGD), so as to improve the management of the disease and improve the quality of life of the patients.Methods:Clinical data of 82 children with CGD hospitalized at Children′s Hospital of Chongqing Medical University and born between January 1999 and December 2016 were collected.Patients were divided into the survival group and the death group.The general information, infectious events and inflammatory complications, as well as treatments and survival situations were analyzed.Results:Among the 82 cases, 55 cases (67.1%) were in the survival group and 27 cases (32.9%) were in the death group.Forty-nine (59.8%) cases developed manifestations in the neonatal period.Specifically, there was a statistically significant difference ( P<0.05) in the proportion of patients who deve-loped manifestations in the neonatal period between the death group (81.5%) and the survival group (49.1%). Fifty-eight (70.7%) cases started to receive Compound Sulfamethoxazole since diagnosis, with an average duration of 36.8 months.Fifty-two (63.4%) cases received Voriconazole or Itraconazole to prevent fungal infection, with an average duration of 34.3 months.There were 288 hospitalizations due to infections in total.The detection rate of bacteria, fungi and mycobacterium tuberculosis was 41.3%, and the rate in the death group (51.8%) was higher than that in the survival group (36.9%)( P<0.05). Klebsiella pneumoniae, Staphylococcus aureus, Burkholderia onion and Escherichia coli were the most frequent bacteria detected, among which Klebsiella pneumoniae and Escherichia coli were all exten-ded-spectrum β-lactamases positive.The use of advanced-antibiotics in the death group (70.4%) was higher than that in the survival group (40.0%) ( P<0.05). Seventeen (20.7%) cases developed inflammatory complications, mainly including interstitial lung disease or pulmonary fibrosis, inflammatory bowel disease and incomplete Kawasaki disease.Thirty-two (39.0%) cases received hematopoietic stem cell transplantation (HSCT), of which 25 patients (78.1%) were transplanted in Children′s Hospital of Chongqing Medical University, with a success rate of 96.0% (24/25 cases). The Kaplan-Meier survival curves showed a worse prognosis in those who developed manifestations in neonates, rely on advanced-antibiotics, and did not receive transplantations. Conclusions:The earlier the clinical manifestations appear, and the higher the utilization rate of advanced-antibiotics used, the more serious the condition is.Conservative treatment with drugs is still insufficient, and the emergence of drug-resistant bacteria increases the difficulty of managements.The recognition and treatments of inflammatory complications needs more explorations.HSCT is so far the only curative therapy for CGD in China.

Case for diagnosis. Eyelid edema and erythematous papules disseminated on the face

Abstract Lupus miliaris disseminatus faciei or acne agminata is a chronic inflammatory disorder of the skin, considered an intriguing entity due to its pathogenesis, which is still largely speculative. It has been linked to tuberculosis, sarcoidosis, rosacea, and other granulomatous diseases, but it is considered an independent entity.

​Clinical Spectrum of Otorhinolaryngological Manifestations in Leprosy: A Retrospective Analysis from Jammu and Kashmir

Introduction: Leprosy is a chronic infectious granulomatous disease caused by Mycobacterium leprae, also known as Hansen’sdisease. The disease affects the peripheral nervous system, skin, and mucous membrane. Dissemination and transmission ofM. leprae are primarily from nasal mucosa of infected persons.Materials and Methods: A record-based retrospective observational study was done in the Department of Dermatology andENT, ASCOMS Hospital, Jammu, Jammu and Kashmir, to know the prevalence of otorhinolaryngological manifestations ofleprosy using records of 49 leprosy patients retrieved for 5 years from 2013 to 2018.Results: Forty-nine patients with 40 (82%) males and 9 (18%) females were included in the study having male–to-female ratio4.5:1. A majority of the patients (47%) were in the age group of 20–40 years. Forty-seven (96%) patients had a multibacillarytype of leprosy, while only 2 (4%) patients had paucibacillary leprosy. Seven (14%) patients showed reaction. Four (8%) showedtype I and 3 (6%) showed type II reaction. Nasal manifestations were predominantly encountered among the otorhinolaryngealmanifestations. All the otorhinolaryngeal manifestations were in the multibacillary type of leprosy. The main nasal symptomswith which patients presented were nasal stuffiness (14%), crust formation (8%), and recurrent mild epistaxis (6%). On anteriorrhinoscopy, mucosal changes (pale mucosa and edema) and nasal crusting were seen in 7 (14%) patients, atrophic conchawas seen in 3 (6%) patients and ulceration of the septal perforation was seen in 2 (4%) patients. Saddle nose deformity wasseen in 1 patient. Among the otological manifestations, two patients had erythematous nodules on pinna, while diffuse infiltrationof ear lobules was noted in five patients. Labial edema was seen in two patients and nodular lesion on the lip in one patient.Conclusion: Among the otorhinolaryngological manifestations, nasal involvement was the most commonly seen in leprosypatients. An otolaryngological examination should be routinely done in the diagnosed patients of leprosy

Avances en el diagnóstico de la enfermedad granulomatosa crónica: primer estudio familiar en Cuba / Advances in the diagnosis of chronic granulomatous disease: the first family study in Cuba

Introducción: La enfermedad granulomatosa crónica es una inmunodeficiencia primaria causada por mutaciones en la enzima NADPH oxidasa. Esta compromete la producción de especies reactivas del oxígeno, que son importantes contra patógenos. La prueba de la oxidación de la dihidrorodamina es un método eficaz para diagnosticar la enfermedad. Objetivo: Demostrar la utilidad de la prueba de la oxidación de la dihidrorodamina y del patrón de herencia en la confirmación del diagnóstico de la enfermedad granulomatosa crónica de un paciente. Métodos: Estudio de caso de una familia con diagnóstico de enfermedad granulomatosa crónica. Se tomó muestra de sangre periférica para citometría de flujo a tres individuos. Se realizó la prueba de la oxidación de la dihidrorodamina bajo estímulo con acetato de forbolmiristato y se evaluaron las subpoblaciones linfocitarias. Las muestras se leyeron en un citómetro GALLIOS, Beckman Coulter. Los datos obtenidos se analizaron en el programa informático Kaluza. Resultados: El paciente masculino tuvo un valor de oxidación de la dihidrorodamina positiva de 0,87 por ciento, que confirmó un patrón de herencia ligado al cromosoma X; mientras que la madre y hermana gemela portadoras tuvieron valores de 46,76 por ciento y 37,32 por ciento, respectivamente. Se encontraron alteraciones en las subpoblaciones linfocitarias. Conclusiones: La prueba de la oxidación de la dihidrorodamina es un método muy efectivo, rápido y sencillo que confirma el diagnóstico de la enfermedad granulomatosa crónica y determina el patrón de herencia y fenotipo de la enfermedad. Además, permite identificar a las mujeres portadoras según la distribución de los neutrófilos normales y los que tienen el gen CYBB mutado(AU)

Introduction: Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the NADPH oxidase enzymes. This compromises the production of oxygen reactive species, which are important against pathogens. The dihydrorhodamine oxidation test is an effective method for diagnosing the disease. Objective: To demonstrate the usefulness of the dihydrorhodamine oxidation test and the inheritance pattern in confirming the diagnosis of chronic granulomatous disease in a patient. Methods: A case study of a family with a diagnosis of chronic granulomatous disease. A peripheral blood sample was taken from three individuals and by flow cytometry. The dihydrorhodamine oxidation test was performed under stimulation with phorbolmyristate acetate, and lymphocyte subpopulations were evaluated. The samples were read on a GALLIOS, Beckman Coulter cytometer. The data obtained were analyzed using the computer program Kaluza. Results: The male patient had a positive dihydrorhodamine oxidation value of 0.87 percent, which confirmed an inheritance pattern linked to the X chromosome; while the carrier mother and twin sister had values 8203;8203;of 46.76 percent and 37.32 percent, respectively. Alterations were found in the lymphocyte subpopulations. Conclusions: The dihydrorhodamine oxidation test is a very effective, fast and simple method that confirms the diagnosis of chronic granulomatous disease and determines the inheritance pattern and phenotype of the disease. In addition, it allows the identification of female carriers according to the distribution of normal neutrophils and those with the CYBB mutation(AU)

Renal manifestations of sarcoidosis: from accurate diagnosis to specific treatment

ABSTRACT Sarcoidosis is a multisystem granulomatous disease characterized by epithelioid noncaseating granulomas associated with clinical and radiologic findings. The cause of this disease is still uncertain. Sarcoidosis affects mostly lungs and lymph nodes and is not usually considered a urological disease, therefore, this etiology may be overlooked in several urological disorders, such as hypercalcemia, hypercalciuria and nephrolithiasis. It affects all races and genders. This review aims to describe the urological manifestations of sarcoidosis and to elucidate how the disease may affect the management of numerous urological conditions.

Enfermedad granulomatosa crónica: diagnóstico mediante el ensayo de dihidrorodamina / Chronic granulomatous disease: diagnosis by the dihydrorhodamine assay

Resumen: Introducción: La enfermedad granulomatosa crónica (EGC) se caracteriza por una alteración de la función oxidativa de neutrófilos, presentando herencia ligada al cromosoma X (EGC LX) y autosómica recesiva (EGC AR). El ensayo de dihidrorodamina (DHR) es utilizado para el diagnóstico y detección de portadoras, además proporciona información sobre patrones de herencia. Objetivo: Detectar casos de EGC en niños con infecciones recurrentes y evaluar a sus familiares femeninos mediante el ensayo de DHR, para identificar portadoras y obtener información acerca de posibles patrones de herencia. Pacientes y Método: Fueron incluidos 107 pacientes (<18 años de edad) con sospecha clínica de EGC como neumonías, linfadenopatías y abscesos, remitidos por médicos de hospitales públicos, del 2014 al 2017. Además, se incluyeron seis mujeres, familiares de los niños con EGC. A las muestras de los pacientes se aplicó el ensayo DHR, expresando los resultados como índice de estimulación de neutrófilos (IE). Resultados: La mediana de edad de los pacientes fue de 3 años y 62/107 fueron varones. El IE promedio fue 39,7 ± 13,8 y 101/107 niños exhibieron un cambio completo de fluorescencia de DHR. En 2/107 niños no se observó dicho cambio (IE = 1,0), lo cual indica posible EGC LX, y un tercer niño mostró un leve cambio (IE = 4,8), compatible con EGC AR. En 5/6 mujeres se encontró un patrón bimodal, indicando un estado de portadora. Conclusiones: Fueron detectados tres casos de EGC y cinco portadoras mediante el ensayo de DHR, realizado por primera vez en Paraguay. También se obtuvo información sobre los posibles patrones de herencia, EGC LX en dos familias y un caso probable de EGC AR.

Abstract: Introduction: Chronic granulomatous disease (CGD) is characterized by an alteration of the neutrophil oxidative function. Its inheritance patterns are linked to the X chromosome (X-linked CGD) and autosomal recessive (AR CGD). The dihydrorhodamine (DHR) assay is used for the diagnosis and detection of carriers and provides information on inheritance patterns. Objective: To detect CGD cases in chil dren with recurrent infections and to evaluate their female relatives through the DHR assay to iden tify carriers and obtain information about possible inheritance patterns. Patients and Method: 107 patients (<18 years of age) with clinical suspicion of CGD such as pneumonia, lymphadenopathies, and abscesses were included, referred by physicians from public hospitals between 2014 and 2017. Six female relatives of children with CGD were also included. The DHR assay was performed on all patient samples and the results were expressed as neutrophils stimulation index (SI). Results: The median age of patients was 3 years and 62/107 of them were male. The average SI was 39.7±13.8 and a complete shift of DHR was found in 101/107 children. In 2/107 children, no DHR shift was observed (SI=1.0) indicating possible X-linked CGD, and a third child showed a slight DHR shift (SI=4.8) compatible with AR CGD. 5/6 female relatives presented a bimodal pattern, showing a carrier status. Conclusions: Three cases of CGD and five female carriers were detected through the DHR assay, being the first time that this technique was used in Paraguay. Information on the most likely inheri tance patterns, two X-linked CGD, and one AR CGD case was also obtained.

Cutaneous sarcoidosis: clinico-epidemiological profile of 72 patients at a tertiary hospital in São Paulo, Brazil,

Abstract Background: Sarcoidosis is a multisystem disease of unknown cause that is characterized by the presence of granulomas in various organs. Cutaneous involvement is common and the reported incidence has varied from 9% to 37%. Studies on cutaneous sarcoidosis in Brazil are lacking. Objectives: To describe the clinical and epidemiological aspects of patients with cutaneous sarcoidosis diagnosed at the Department of Dermatology of the University of São Paulo, from May 1994 to March 2018. Methods: Clinical data of patients with confirmed cutaneous sarcoidosis were retrospectively reviewed and classified according to gender, ethnicity, age at diagnosis, cutaneous presentation, systemic involvement and treatment. Results: Cutaneous sarcoidosis was diagnosed in 72 patients with a female predominance (74%). The mean age at diagnosis was 49.6 years and most of the patients were white (61%). Papules and plaques were the most common lesions. Systemic sarcoidosis was detected in 81% of patients, affecting mainly the lungs and thoracic lymph nodes (97%). Typically, cutaneous lesions were the first manifestation (74%). Systemic therapy was necessary for 72% of patients; the dermatologist managed many of these cases. Oral glucocorticoids were the most commonly used systemic medication (92%). The mean number of systemic drugs used was 1.98 per patient. Limitations: Insufficient data in medical records. Conclusions: This series highlights the dermatologist role in recognizing and diagnosing cutaneous sarcoidosis, evaluating patients for systemic disease involvement and treating the skin manifestations. Cutaneous sarcoidosis was once considered exceedingly infrequent in Brazil in comparison to infectious granulomatous diseases; however, the present series seems to suggest that the disease is not so rare in this region.

Síndrome de Löfgren en Neiva - Colombia: reporte de un caso / Löfgren Syndrome in Neiva - Colombia: A Case Report

Resumen La sarcoidosis es una enfermedad inflamatoria granulomatosa multisistémica crónica de etiología desconocida, que afecta en su mayoría a adultos jóvenes. Se presenta el caso de un paciente masculino de 35 años de edad, que asistió a nuestro hospital por un cuadro clínico de fiebre prolongada asociada a poliartritis y eritema nodoso, que fue diagnosticado con síndrome de Löfgren, entidad poco frecuente en nuestro país. A pesar de la baja prevalencia, la sarcoidosis y su variante, síndrome de Löfgren, se deben tener siempre en cuenta en pacientes con eritema nodoso y/o adenopatías hiliares.

Abstract Sarcoidosis is a chronic multisystemic granulomatous inflammatory disease of unknown etiology which affects mainly young adults, characterized by formation of non-caseous granulomas. Löfgren syndrome refers to an acute presentation of sarcoidosis, characterized by the triad of bilateral hilar lymphadenopathies, erythema nodosum and periarticular swelling. This paper presents the case of a 35-year-old man, who attended our hospital with prolonged fever associated to polyarthritis and erythema nodosum. After medical assessment, laboratory test results, X-ray and CT scans, the patient was diagnosed with Löfgren syndrome, a disease seldom encountered in Colombia. Despite the low prevalence of sarcoidosis and Löfgren syndrome in our country, erythema nodosum and/or hilar adenopathies should increase suspicion of this rare disease, and Löfgren syndrome should be considered in patients with this presentation.